Biophysical characterization of the Plasmodium falciparum circumsporozoite protein's N-terminal domain

Protein Sci. 2024 Jan;33(1):e4852. doi: 10.1002/pro.4852.

Abstract

The circumsporozoite protein (CSP) is the main surface antigen of the Plasmodium sporozoite (SPZ) and forms the basis of the currently only licensed anti-malarial vaccine (RTS,S/AS01). CSP uniformly coats the SPZ and plays a pivotal role in its immunobiology, in both the insect and the vertebrate hosts. Although CSP's N-terminal domain (CSPN ) has been reported to play an important role in multiple CSP functions, a thorough biophysical and structural characterization of CSPN is currently lacking. Here, we present an alternative method for the recombinant production and purification of CSPN from Plasmodium falciparum (PfCSPN ), which provides pure, high-quality protein preparations with high yields. Through an interdisciplinary approach combining in-solution experimental methods and in silico analyses, we provide strong evidence that PfCSPN is an intrinsically disordered region displaying some degree of compaction.

Keywords: Plasmodium falciparum; biophysics; circumsporozoite protein; intrinsic disorder; recombinant protein production and purification; structural biology.

MeSH terms

  • Antimalarials*
  • Humans
  • Malaria Vaccines* / chemistry
  • Malaria Vaccines* / metabolism
  • Malaria, Falciparum*
  • Plasmodium falciparum / genetics
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / genetics

Substances

  • Malaria Vaccines
  • Protozoan Proteins
  • Antimalarials